A microbial compound in the gut can lead to anxiety-producing behaviors, Nature finds

A Caltech-led team has found that a small-molecule metabolite produced by bacteria in the guts of mice can enter the brain and alter the function of brain cells, leading to increased anxiety in the mice

The research was conducted primarily in the labs of Sarkis Mazmanian, Luis B.

Decades of research have shown that the bacterial community (the microbiome) in an animal's gut influences the immune system and metabolism; research over the past few years has linked the microbiome to brain function and mood

"It's hard to prove a causal relationship between what's happening in the gut and in the brain, not just disease states and the presence or presence of certain microbes," said Brittany Needham, first author of the new study and a postdoctoral scholar in Mazmanian's lab.

The study focused on a bacterial metabolite (a byproduct of microorganisms) called 4-ethylphenyl sulfate (4EPS)

In this work, the team focused on the effects of 4EPS on a mouse model of anxiety

The study compared two groups of laboratory mice: One group of mice was implanted with a pair of bacteria genetically engineered to produce 4EPS; the bacteria in the control group of mice were identical except that they lacked the ability to produce 4EPS

Compared with non-4EPS mice, mice with 4EPS spent less time exploring the area and more time hiding, suggesting they had higher levels of anxiety

Taking a closer look at the brain cells within these altered areas, the team found changes in specialized cells called oligodendrocytes

However, when 4EPS mice were treated with a drug known to increase oligodendrocyte myelin production, the drug was able to overcome the negative effects of 4EPS—the mice regained normal myelin production and reduced anxiety behaviors

In a related study, also published in the journal Nature Medicine, the researchers showed that the absorption and removal of 4EPS from the system of mice with an oral drug reduced anxiety behaviors

"This is an exciting proof-of-concept finding that a specific microbial metabolite alters the activity and complex behavior of brain cells in mice, but how this happens is still unknown," Mazmanian said

Next work examines the mechanism by which 4 eps affects oligodendrocytes—which proteins might interact with, and whether 4 eps directly affects changes in the brain, or if it is affecting another part of the body, these effects make their brains

article title

A gut-derived metabolite alters brain activity and anxiety behaviour in mice